Cancer cells exhibit altered cellular metabolism in order to promote growth and proliferation. Cells harboring oncogenic lesions that result in hyperactivated c-Myc (Myc) are characterized by an increased demand for the nutrients glucose and glutamine, which are used by the cell to generate energy and to supply metabolic precursors for anabolic processes. A hallmark of Myc-driven cancers is an increase in global translation, one of the most energetically expensive processes in the cell.
Cancer cells display upregulation of nucleotide biosynthetic pathways to meet the demands of growth and proliferation. Indeed, many chemotherapies exist that inhibit enzymes responsible for nucleotide production. However, numerous problems still remain regarding the effectiveness of these drugs in the clinic. For instance, significant side effects are associated with many nucleotide biosynthesis inhibitors. Additionally, some cancers develop mechanisms of resistance to nucleotide biosynthesis inhibitors, rendering them ineffective altogether.
Thus, there remains a need for therapeutic methods that target the nucleotide biosynthetic pathway. The present invention addresses this need and others.